IPF-PRO Registry Continues to Shed Light on Devastating Lung Disease

May 18, 2020 – The registry, which has enrolled 1,002 patients with idiopathic pulmonary fibrosis, shares critical knowledge and insights to help combat lung disease.

Clinical researchers at the DCRI continue to uncover new information about idiopathic pulmonary fibrosis (IPF), a devastating, progressive lung disease with an unknown cause, by analyzing data collected through the IPF-PRO/ILD-PRO Registry.

The registry is sponsored by Boehringer Ingelheim (BI) and includes more than 1,000 patients with IPF. The registry’s principal investigator is Scott Palmer, MD, MHS. Other members of the DCRI team include Laurie Snyder, MD, MHS; Jamie Todd, MD; Megan Neely, PhD; Eric Yow, MS; Emily O’Brien, PhD; and Rosalia Blanco, MBA. Work with the registry has been ongoing since 2014 and has, to date, resulted in eight published manuscripts and 40 poster or abstract presentations. Below is a sampling of published findings from the past several months.

“Thanks to the partnership with BI and collaborative efforts of our DCRI team and site investigators over the last six years, we’ve made great progress in improving our understanding of idiopathic pulmonary fibrosis,” Palmer said. “We have been able to rapidly share the knowledge we gain through this registry in order to understand the impact of the disease and its mechanisms and to guide the development of new and improved approaches to patient care and treatment.”

Potential Biomarkers Could Help in Diagnosis, Outcome Predictions

Because timely diagnosis and management of IPF are both challenges, much of Todd’s research focuses on determining whether there are biomarkers that could help clinicians in diagnosis, prognosis, or predicting how patients will respond to treatment. In addition, these highly translational studies are providing new and fundamental insights into IPF disease mechanisms by leveraging the unique biosamples prospectively collected among patients enrolled in the registry.

A recent study led by Todd and published in BioMed Central Pulmonary Medicine compared blood samples of patients enrolled in the IPF-PRO Registry with the blood of patients without lung disease. The study, which quantified the expression of a broad array of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), shed light on how the expression of single MMPs and TIMPs relates to status and severity of IPF. However, because almost all of the MMPs and TIMPs presented in elevated levels in patients with IPF, the study also sought to show how combinations of MMPs and TIMPs aid in diagnosis or prognosis in patients with IPF. Although further validation of the study’s results will be necessary, Todd said, this study is a step toward identifying biomarkers that could be useful in future diagnosis and treatment of IPF.

Other DCRI contributors to this study include Palmer, Neely, and Robert Overton. Duke’s L. Kristin Newby, MD, is principal investigator of the MURDOCK study, which provided the control group for this study and contributed to the publication.

Proteins in Plasma Found to be Associated with Death, Lung Transplant

Another study led by Todd found that, when considered along with clinical factors such as forced vital capacity and diffusion capacity, 65 proteins were significantly associated with the composite outcome of death or lung transplant. When proteins were considered without clinical factors, a set of 55 proteins could be used to predict the probability of respiratory death or lung transplant.

The study examined proteins in the plasma of 300 IPF-PRO Registry participants who had cases diagnosed or confirmed within a six-month timeframe. An abstract detailing the study was accepted at American Thoracic Society’s annual conference (ATS 2020) and was published in the ATS abstract edition of the American Journal of Respiratory and Critical Care Medicine online after the conference was canceled due to COVID-19. Neely and Palmer also contributed to this study, and Overton and Hillary Mulder, MS, provided statistical support.

Insights on Time to Diagnose IPF

A study led by Snyder studied a cohort of IPF-PRO participants to determine how long it took for patients to receive an IPF diagnosis after the first symptom onset or imaging evidence of pulmonary fibrosis. The study also compared the time from enrollment in the registry to death or lung transplant between the two groups of patients. An abstract detailing the study accepted at ATS 2020 and was published in the ATS abstract edition of the American Journal of Respiratory and Critical Care Medicine online. Neely, Hellkamp, and DCRI fellow Christopher Mosher, MD, also contributed to this study.

Measures of IPF Severity Correspond to Patient-Reported Quality of Life

A study led by O’Brien and published in Chest examined the associations between objective disease severity measures collected as part of the IPF-PRO Registry—such as diffusing capacity for carbon monoxide, oxygen use at risk and with activity, and an index score determined by age, gender, and lung function—and patient-reported quality of life measures based on a questionnaire.

The study found that quality of life was worse in patients enrolled in IPF-PRO compared with the general population. Increasing disease severity was also associated with worse quality of life. Other DCRI contributors include Snyder; Todd; Palmer; Neely; Aparna Swaminathan, MD; and Anne Hellkamp, MS.

Expanding on the IPF-PRO Registry Model

A related group of respiratory illness that needs further investigation is the broader category of interstitial lung disease (ILD) other than IPF, as it is now clear a subset of these patients develop a relentless and progressive fibrosis similar to patients with IPF.

Building on the success of the IPF-PRO Registry, the DCRI, again in partnership with BI, expanded the registry to include patients with ILD who demonstrate evidence of progressive fibrosis. The ILD-PRO Registry, which will also be led by Palmer and the same leadership from the DCRI team, will enroll approximately 1,000 patients with ILDs across 45 sites nationwide, drawing on the infrastructure already established by the IPF-PRO Registry. An abstract detailing the design of the ILD-PRO Registry was accepted at ATS 2020 and was also published in the ATS abstract edition of American Journal of Respiratory and Critical Care Medicine online.

Neely, Snyder, O’Brien, and Todd also contributed to this abstract and will serve as co-investigators on the ILD-PRO Registry. Todd is the biomarker committee co-chair and Snyder is the publication committee co-chair for all of the registry studies.

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